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111.
Yamane N Tozuka Z Sugiyama Y Tanimoto T Yamazaki A Kumagai Y 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,858(1-2):118-128
A sample treatment procedure and high-sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for quantitative determination of fexofenadine in human plasma was developed for a microdose clinical trial with a cold drug, i.e., a non-radioisotope-labeled drug. Fexofenadine and terfenadine, as internal standard, were extracted from plasma samples using a 96-well solid-phase extraction plate (Oasis HLB). Quantitation was performed on an ACQUITY UPLC system and an API 5000 mass spectrometer by multiple reaction monitoring. Chromatographic separation was achieved on an XBridge C18 column (100 mm x 2.1 mm i.d., particle size 3.5 microm) using acetonitrile/2 mM ammonium acetate (91:9, v/v) as the mobile phase at a flow rate of 0.6 ml/min. The analytical method was validated in accordance with the FDA guideline for validation of bioanalytical methods. The calibration curve was linear in the range of 10-1000 pg/ml using 200 microl of plasma. Analytical method validation for the clinical dose, for which the calibration curve was linear in the range of 1-500 ng/ml using 20 microl of plasma, was also conducted. Each method was successfully applied for making determinations in plasma using LC/ESI-MS/MS after administration of a microdose (100 microg solution) and a clinical dose (60 mg dose) in eight healthy volunteers. 相似文献
112.
The phenylboronic acids substituted with an azo group on the ortho-position show a significant change in UV-vis spectra upon sugar binding. A new mechanism for the spectral change of the dyes is proposed based on the formation and cleavage of B-N dative bond between boronic acid group and azo group. 相似文献
113.
Yamazaki KG Villarreal FJ 《American journal of physiology. Heart and circulatory physiology》2011,300(4):H1282-H1290
Perturbations in the normal sequence of ventricular activation can create regions of early and late activation, leading to dysynchronous contraction and areas of dyskinesis. Dyskinesis occurs across the left ventricular (LV) wall, and its presence may have important consequences on cardiac structure and function in normal and failing hearts. Acutely, dyskinesis can trigger inflammation and, in the long term (6 wk and above), leads to LV remodeling. The mechanisms that trigger these changes are unknown. To gain further insight, we used a canine model to evaluate transumural changes in myocardial function and inflammation induced by epicardial LV pacing. The results indicate that 4 h of LV suprathreshold pacing resulted in a 30% local loss of endocardial thickening. Assessment of neutrophil infiltration showed a significant approximately fivefold increase in myeloperoxidase activity in the epicardium versus the midwall/endocardium. Matrix metalloproteinase-9 activity increased ~2 fold in the epicardium and ROS generation increased ~2.5-fold compared with the midwall/endocardium. To determine the effects that electrical current alone has on these end points, a group of animals was subjected to subthreshold pacing. Significant increases were observed only in epicardial myeloperoxidase levels. Thus, the results indicate that transmural dyskinesis induced by suprathreshold epicardial LV activation triggers a localized epicardial inflammatory response, whereas subthreshold stimulation appears to solely induce the trapping of leucocytes. Suprathreshold pacing also induces a loss of endocardial function. These results may have important implications as to the nature of the mechanisms that trigger the inflammatory response and possibly long-term remodeling in the setting of dysynchrony. 相似文献
114.
Higo S Hojo Y Ishii H Komatsuzaki Y Ooishi Y Murakami G Mukai H Yamazaki T Nakahara D Barron A Kimoto T Kawato S 《PloS one》2011,6(7):e21631
Background
Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC) synthase, cytochrome P450(c21).Methodology/Principal Findings
The expression of P450(c21) was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG) was demonstrated by metabolism analysis of 3H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21), P450(2D4), P450(11β1) and 3β-hydroxysteroid dehydrogenase (3β-HSD) were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT) and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM) doses of CORT for 1 h.Conclusions/Significance
These results imply the complete pathway of corticosteroid synthesis of ‘pregnenolone →PROG→DOC→CORT’ in the hippocampal neurons. Both P450(c21) and P450(2D4) can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands. 相似文献115.
New and effective method for the Beckmann rearrangement of indanone oxime mesylate is described, in which a selective and controlled production of the isomeric isocarbostyrils is achieved. 相似文献
116.
Tanaka M Sagawa S Hoshi J Shimoma F Yasue K Ubukata M Ikemoto T Hase Y Takahashi M Sasase T Ueda N Matsushita M Inaba T 《Bioorganic & medicinal chemistry》2006,14(17):5781-5794
Conformationally restricted 3-anilino-4-(3-indolyl)maleimide derivatives were designed and synthesized aiming at discovery of novel protein kinase Cbeta (PKCbeta)-selective inhibitors possessing oral bioavailability. Among them, compounds having a fused five-membered ring at the indole 1,2-position inhibited PKCbeta2 with IC50 of nM-order and showed good oral bioavailability. One of the most potent compounds was found to be PKCbeta-selective over other 6 isozymes and exhibited ameliorative effects in a rat diabetic retinopathy model via oral route. 相似文献
117.
H Miyata H Hayashi S Suzuki N Noda A Kobayashi H Fujiwake M Hirano N Yamazaki 《Biochemical and biophysical research communications》1989,163(1):500-505
Isolated rat heart myocytes were loaded with both the Ca2+ sensitive fluorescent probe fura-2/AM and the fluorescent pH indicator 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF/AM). Changes in [Ca2+]i and pHi were measured simultaneously using digitized video fluorescence microscopy. In measurement of [Ca2+]i and pHi, the ratios of dual-loaded cells were not different from single-loaded cells. Using this method, [Ca2+]i and pHi in myocytes were 48 +/- 7 nM and 7.17 +/- 0.05. It is concluded that [Ca2+]i and pHi could be measured simultaneously in isolated myocyte using dual-loading of fura-2 and BCECF. 相似文献
118.
119.
We previously reported that serum deprivation stimulates myofibrillar proteolysis in chick myotubes. In the present study, we examined the effect of serum deprivation on expression of the proteolytic-related genes (ubiquitin, proteasome, calpains, and cathepsin B) by real-time PCR of cDNA in chick myotubes. Myotubes were incubated with serum-free medium for 24 h. Ubiquitin and proteasome subunits (C1 and C2) and calpains (m-, mu-, and p94/calpain-3) but not cathepsin B mRNA expression were increased by serum deprivation. These results indicate that serum deprivation stimulates ubiquitin-proteasome and calpain proteolytic pathways, resulting in an increase in myofibrillar proteolysis in chick myotubes. 相似文献
120.
Ueda S Terauchi H Suzuki K Yano A Matsumoto M Kubo T Minato H Arai Y Tsuji J Watanabe N 《Bioorganic & medicinal chemistry letters》2005,15(5):1361-1366
We have previously reported that (4R,5R)-5-ethyl-2-imino-4-methylthiazolidine (3) strongly inhibits inducible nitric oxide synthase (iNOS). In a successive search for strong and selective iNOS inhibitors, we, herein, describe the synthesis of the selenium analogue of 3 (4: ES-2133) and its related optically active compounds and examine their in vitro and in vivo inhibitory activity against iNOS. In addition, an alternative synthetic method to the selected compound 4 and its pharmacokinetic profile is also reported. 相似文献